1. Technical Field
The present invention relates to an array-type-transducer-based high-power ultrasound delivery system and, more particularly, to an array-type macromolecule delivery system based on high-power ultrasound and microbubbles.
2. Description of Related Art
The technical development and applications of high-power ultrasound in the medical equipment industry, among others, have reached a highly mature stage. Ultrasound transducers and emission control systems are also well-known and mature technologies. As the biomedical effects of ultrasound in medical applications are correlated to the initial mode, acoustic power, and emission duration of the ultrasound employed, the US Food and Drug Administration (FDA) has set up regulations in this regard.
Conventionally, when ultrasound is applied to a cell-containing nutrient broth in a Petri dish, a physical phenomenon known as “inertial cavitation” takes place in the ultrasound-conducting liquid medium. Briefly stated, when ultrasound is transmitted through an ultrasound-conducting liquid medium, the energy of the ultrasound causes the liquid molecules to produce countless vacuum bubbles, which expand rapidly and collapse as soon as the surface of the bubbles can no longer resist the external liquid pressure.
More specifically, when the acoustic pressure of the ultrasound in the ultrasound-conducting liquid medium accumulates to a certain level, the bubbles begin to expand and are squeezed and closed in the positive-pressure area. When the countless tiny vacuum bubbles in the ultrasound-conducting liquid medium eventually implode violently due to compression and rarefaction in the oscillating process, the breaking bubbles accelerate and hence make a huge impact (up to thousands of atmospheres of pressure locally) on the membranes of the cells. Such a strong impact not only can enhance the permeation of macromolecules (e.g., plasmid DNA, particles, and drug molecules) through the cell membranes, but also forms microscopic pores on the membranes, the latter process called “sonoporation”. The micropores on the cell membranes will disappear in 24 hours, thus bringing the membranes back to their original state.
Sonoporation is very likely to be a result of the inertial cavitation mechanism, and this physical property has given rise to the development of the ultrasonic microbubble-based delivery method in the 1990s, with a view to achieving gene delivery through sonoporation. This microbubble-based method can be used to deliver macromolecules such as plasmid DNA, functional genes, particles, drug molecules, or even nanoparticles to various types of cells, including, for example, primary cells, stem cells, endothelial progenitor cells, or cell lines.
However, in the case of ultrasonic microbubble-based delivery systems that are designed to deliver macromolecules to cells of various types, all the systems in the literature and currently available on the market—be they of the continuous wave or pulsed wave type, and regardless of whether they are for commercial use or are self-made systems—are high-power ultrasound systems with a single-element ultrasound transducer. In other words, only one transducer is used in each system to perform ultrasonic radiation.
Since an ultrasound system with a single-element ultrasound transducer can only perform ultrasonic radiation on one culture well at a time, the entire operation, which typically involves a plurality of culture wells, is disadvantageously time-consuming and labor intensive. Moreover, as the ultrasound transducer is manually lowered into each culture well, the depth by which the ultrasound transducer dips into the ultrasound-conducting liquid medium cannot be standardized, nor can the radiation time be quantified. These add to the drawbacks of the conventional ultrasound systems.